The objectives of the proposed research are to study the metabolism of xenobiotic compounds by fish and to determine the functional significance of these pathways. The work will focus upon the metabolism and disposition of carbaryl, 2,4-D, 2,4-D-butyl ester, diethylhexylphthalate (DEHP), 3-trifluoromethyl-4-nitrophenol (TFM) and 2,5,2',5'tetrachlorobiphenyl (PCB) in salmonides. If biotransformation of these compounds in fish leads to less toxic compounds and the reactions proceed at significant rates, blockade of their metabolism by known specific inhibitors would be expected to increase the acute toxicity (LC 50) of the compound in question. On the other hand, if these biotransformation enzymes are inducible as are the mammalian microsomal enzymes, pre-exposure of fish to inducing agents may be expected to decrease the toxicity of the compound being studied. The information gleaned from these biotransformation studies may lead to the mechanisms of species selectivity of many water borne pollutants in addition to providing data necessary for residue analysis of metabolites of foreign compounds as well as the parent molecule. In general, the experimental approach involves determination of the acute toxicity (LC 50) of the above compounds in trout, studying the metabolism of each compound and determining if the acute toxicity is altered by known inhibitors and inducers of microsomal drug metabolizing enzymes. Special attention will be given to the possibility of alteration of these metabolic processes by inducers and inhibitors which may be present in the aqueous environment such as DDT and the polychlorinated biphenyl compounds and piperonyl butoxide. BIBLIOGRAPHIC REFERENCES: Statham, Charles N., Pepple, Sharon K. and Lech, John J.: Biliary excretion products of l-(l-C14)naphthyl-N-methylcarbamate (carbaryl) in rainbow trout (Salmo gairdneri). Drug Metabolism and Disposition 3: 400-406, 1975. Statham, Charles N. and Lech, John J.: Potentiation of the acute toxicity of several pesticides and herbicides in trout by carbaryl. Toxicology and Applied Pharmacology 34: 83-87, 1975.